Uracyst® is a sterile solution of 2% chondroitin sulfate (400 mg) in a 20 mL vial. In clinical trials, Uracyst has proven to be effective after 6 and 10 instillations (Nickel et al.), has proven to restore the barrier function (Hurst et al.) and potentially provides the optimum concentration in a single instillation to effective saturate the human IC bladder (Hurst et al.)
Two subsequent pilot RCTs offered varying degrees of success, neither of which reached statistical significance. A meta-analysis of these three studies has been performed and the conclusion was very positive for the use of Uracyst® in the management of IC (Nickel et al.)
In the countries where Uracyst® is available, there have been over 100,000 instillations. Uracyst® is sold in Canada, is CE marked and sold throughout Europe as well as South Korea.
The importance of chondroitin sulfate in the GAG layer of the urinary bladder.
Chondroitin sulfate is an acidic mucopolysaccharide and is one of the glycosaminoglycans (GAGs). Its repeating disaccharide unit is made up of two simple sugars, namely a glucuronic acid and a galactosamine with one negatively charged hydrophilic sulfate group.
The luminal surface of the bladder is coated with a dense layer of GAGS that provide a protective, impermeable barrier. This surface GAGs are predominantly composed of chondroitin sulfate, dermatan sulfates and heparin sulfates. As a result of the previously mentioned negative electric charge, GAGs on the surface will attract water molecules from the urine and bind them tightly to these sulphur molecules. This creates a highly hydrophilic environment that greatly contributes to the protective impermeability function of the surface GAG layer. This GAG layer protects the underlying tissue from the K+ ions and proteases ever present in the normal urine. Experimental studies done in the USA and presented at the American Urology Association meeting (AUA 2009) provided evidence that Uracyst® repairs the damage to the GAG layer and helps re-establish the impermeable barrier layer of defense in the bladder.
The rational for using chondroitin sulfate in the treatment of IC/PBS
A functional deficiency in the bladder GAG can lead to increased IC symptoms in as many as 60% - 70% of patients.
The dense protective layer known as the GAG protects the underlying tissue from irritation by the noxious substances found in normal urine. In a bladder without an intact GAG layer, these K+ ions and proteases can penetrate deeper into the bladder layer where they may activate sensory nerves. This penetration can cause inflammation, up-regulation of the sensory nerves and lead to the classic symptoms of IC/PBS, pain, urgency and frequency.
The use of a GAG replenishment therapy, such as Uracyst®, can help restore the protective barrier layer and reduce the impact on the underlying bladder tissue and allow the bladder to heal. This activity reduces the symptoms of IC/PBS.
Uracyst has proven to be well tolerated and has been in use since the early 2000’s in Canada and Europe. Uracyst is not systemically absorbed in the blood (Kumar NW.AUA 2009) and no serious adverse events have been reported. Some patients have experienced discomfort from the catheterization process or the catheter lubricants.